September 4, 2008 — A nationwide team of scientists, including researchers at the University of North Carolina at Chapel Hill’s Lineberger Comprehensive Cancer Center, have reported the first results of a large-scale, comprehensive study of the most common form of brain cancer, glioblastoma.

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The findings from the study – conducted by the Cancer Genome Atlas Research Network, a collaborative effort involving 18 institutions and organizations across the country – appeared Thursday (Sept. 4) in the online edition of the journal Nature. The network is funded by the National Cancer Institute and the National Human Genome Research Institute of the National Institutes of Health.

The paper describes the discovery of new genetic mutations and other types of DNA alterations that have potential implications for the diagnosis and treatment of glioblastoma.

More than 21,000 people are estimated to develop brain cancer in the United States each year, and more than 13,000 people will die from the disease. Glioblastoma, the type of brain cancer most often found in adults, is a very fast-growing type of tumor. Most patients die within about 14 months of diagnosis.

Scientists discovered three previously unrecognized genetic mutations that occur with significant frequency, and made an unexpected observation that points to a potential mechanism of resistance to a common chemotherapy drug used to treat brain cancer.

The researchers also identified and mapped major gene interaction pathways that are disrupted in this type of brain cancer. They said that the pathway mapping promises to be particularly informative for scientists developing therapeutic strategies aimed more precisely at specific cancers, or that are better tailored to each patient’s particular tumor subtype.

The network’s members analyzed 206 complete sets of DNA, or genomes, of tumor samples donated by patients with glioblastoma. Each affiliate performed unique genomic assays, which were then combined together to yield new insights. Lineberger scientists Charles Perou, Ph.D., Michael Topal, Ph.D., and Neil Hayes, M.D., performed the genomic, or so-called gene expression assays on the samples. This analysis identified which genes are expressed, or “on”, an important step in identifying the genes linked to brain cancer.

The combined efforts created an unparalleled look at the events that cause glioblastoma tumors to develop, researchers said.

“The ability to look at all genes at once with so many different approaches has never been done before, and the picture painted by this massive data is so rich that it will take us many years to understand fully the data we have collected,” said Perou, also associate professor in the departments of genetics and of pathology and laboratory medicine in the School of Medicine. “This is a very big step towards a comprehensive analysis of the brain cancer genome, which we hope will make an impact upon patient care and improve outcomes.”

Hayes, assistant professor in the hematology and oncology division in the School of Medicine’s department of medicine, said that the collaborative nature of the study would make it possible to detect far more complicated interactions between the genetic events that initiate and spread tumors. “Since these events are different in different patients, it is a real step towards designing personalized therapies,” he said.

Topal, also a professor in the departments of pathology and biochemistry and biophysics in the School of Medicine, said: “The role being played by UNC scientists and core facilities in this groundbreaking cancer study speaks volumes about the wonderful investment being made in cancer research by the people of North Carolina.”

UNC’s chief of neurosurgery and the leader of Lineberger’s neuro-oncology program, Matthew Ewend, M.D., said there is great promise in the network’s approach.

“The glioblastoma remains one of the most significant challenges in cancer therapy,” he said. “The tumor attacks the brain, and has been resistant to many therapies that have had success in treating cancer elsewhere in the body. This important work looks to unlock the secrets of resistance hidden inside the genes of the glioblastoma, and then use these discoveries to develop treatments that attack the weaknesses of the tumor. It’s crucial work that has many positive benefits for our patients.”

The work detailed in the Nature article complements and expands upon a parallel study by John Hopkins researchers of 22 glioblastoma tumors, also published Thursday in the journal Science.

The lead authors of the Nature paper were Lynda Chin, M.D., and Matthew Meyerson, M.D., Ph.D., of Dana-Farber Cancer Institute and Harvard Medical School, Boston. Meyerson is also affiliated with the Broad Institute of MIT and Harvard, Cambridge, Mass.